Semaglutide (E.g. Ozempic / Wegovy) and other mimics of body's GLP-1 hormone used for weight loss

What is semaglutide used for and how does it work?

Semaglutide is the the generic name for a number of drugs taken to regulate blood sugar, INSULIN production, and appetite. Originally prescribed to control type-2 diabetes and obesity, it is now commonly used as an effective tool for losing weight, although not approved by the FDA for such use.

Semaglutide medications mimic a hormone in our body called glucagon-like peptide-1 (GLP-1). In response to food intake, this peptide GLP-1 hormone (a chain of 30 or 31 amino acids) is secreted by L cells in the small intestine (distal [far] end of ileum) and colon, where it is absorbed into the bloodstream. GLP-1 takes action when “docking onto” GLP-1 receptors on cell membranes. Semaglutide (and other GLP-1 mimics) provide a so-called GLP-1 receptor agonist, which has the same effect as natural GLP-1 in activating GLP-1 receptors.

GLP-1 affects several body organs and body systems, muscles and fat cells

GLP-1 can have direct or indirect effects

Brain

After crossing the blood-brain-barrier, GLP-1 signals the brain’s hypothalamus gland to release hormones that:

Reduce food intake, curb appetite and increase satiety
Negatively affects palatability
Provides some neuroprotection

Pancreas

GLP-1 increases synthesis and secretion of INSULIN

Increases survival and proliferation of β-cells and reduces their apoptosis (natural cell death). β-cells produce and secrete INSULIN and amylin (responsible for gastric emptying and curbing appetite)

Reduces release of glucagon (storage form of glucose)

Heart

Increases contractility and heart-rate
Vascular protective effect

Kidney

Mild natriuresis. Sodium excretion in urine, sodium leaving circulation lowers blood volume, as it drags water with it into urine.

Gastrointestinal tract

Reduces motility, gastric emptying, and acid secretion

Muscle

GLP-1 Increases INSULIN sensitivity and glucose uptake

Fat cells

GLP-1 Increases glucose uptake
Increases fat cell breakdown (lipolysis)

Common side-effects of taking semaglutide

Dehydration
Vomiting
Constipation
Diarrhea

Possible mental health side-effects when taking semaglutide

Anxiety, depression or suicidal thoughts, feeling overwhelmed, unwarranted crying

According to NPR.org, FDA’s Adverse Event Reporting System (FAERS) – a voluntary reporting system by patients, medical professionals and caregivers provides a useful tool as an alert for abnormalities), received 489 reports of patients experiencing anxiety, depression or suicidal thoughts while taking semaglutide drugs. In 96 of those reports, the patient had suicidal thoughts. Five of them died. These reports simply provide a database for further study, they do not substantiate a cause. Wegovy lists anxiety, depression and suicidal thoughts as possible side-effects on its label.